Korean ginseng: Clinical Use

In the scientific arena, ginseng and the various ginsenosides are used in many forms and administered via various routes. This review will focus primarily on those methods commonly used in clinical practice.

CANCER PREVENTION

The various anticancer actions of Panax ginseng, as demonstrated in animal and in vitro trials, support its use as an agent to prevent the development and progression of cancer. A 5-year prospective study of 4634 patients over 40 years of age found that ginseng reduced the relative risk of cancer by nearly 50%.

A retrospective study of 905 case-controlled pairs taking ginseng showed that ginseng intake reduced the risk of cancer by 44% (odds ratio equal to 0.56). The powdered and extract forms of ginseng were more effective than fresh sliced ginseng, juice or tea. The preventative effect was highly significant (P < 0.001). There was a significant decline in cancer occurrence with increasing ginseng intake (P < 0.05).

Epidemiological studies in Korea strongly suggest that cultivated Korean ginseng is a non-organ-specific human cancer preventative agent. In case-control studies, odds ratios of cancer of lip, oral cavity and pharynx, larynx, lung, oesophagus, stomach, liver, pancreas, ovary and colorectum were significantly reduced by ginseng use. The most active compounds are thought to be ginsenosides Rg3, Rg5 and Rh2.

Ginseng polysaccharide (18 mg/day) has also been shown to be effective in improving immunological function and quality of life in elderly patients with non-small cell lung cancer.

Chemotherapy

Overexpression of P-glycoprotein or multidrug resistance-associated protein may lead to multidrug resistance of cancer cells. Protopanaxatriol ginsenosides have been shown to sensitise cancer cells to chemotherapeutic agents in vitro by increasing the intracellular accumulation of the drugs through direct interaction with P-glycoprotein. The ginsenoside Rh2 possesses strong tumour-inhibiting properties and sensitises multidrug-resistant breast cancer cells to paclitaxel and animal models demonstrate a synergistic antitumour effect for ginseng acidic polysaccharides and paclitaxel.

Panax ginseng polysaccharide (12 mg IV daily) has also been trialled during treatment for ovarian cancer and the authors suggest that it is ‘effective, safe and reliable for reducing the toxic effects of chemotherapy’.

DIABETES

The putative effects of Korean ginseng on blood glucose and lipid regulation, oxidative stress, and protein glycation suggests a possible role as an adjunctive therapy in the management of diabetes and diabetic complications.

A double-blind, placebo-controlled study with 36 subjects found that 200 mg ginseng elevated mood, improved psychophysical performance and reduced fasting blood glucose and body weight in patients with newly diagnosed type 2 diabetes.

CARDIOVASCULAR DISEASE

Although there are reports of ginseng causing hypertension, red ginseng is actually used as an antihypertensive agent in Korea.

Acute administration of an aqueous preparation of Korean ginseng (100 mg/kg body weight) to 12 healthy, non-smoking male volunteers resulted in an increase in NO levels and a concomitant reduction in mean blood pressure and heart rate.

Ginseng is often used in practice as an adjuvant to both conventional and CAM treatments. An open clinical study of 44 hypertensive patients found red ginseng, 1.5 g three times daily (4.5 g/day), to be useful as an adjuvant to antihypertensive medication. A combination of red ginseng and digoxin was found to be more beneficial than either drug alone in an open study of advanced congestive heart failure. There were no adverse reactions. A combination of ginseng and ginkgo extracts has been found to improve circulation and lower blood pressure in a controlled single-dose study of 10 healthy young volunteers.

Korean red ginseng has also been shown to improve vascular endothelial function in patients with hypertension. The effect is thought to be mediated through increasing the synthesis of nitric oxide.

HYPERUPIDAEMIA

In a small trial of eight males receiving 2 g Panax ginseng extract three times daily (total PGE 6 g/day) for 8 weeks, serum total cholesterol, LDL, and triglyceride concentrations were decreased by 12%, 45% and 24%, respectively and a 44% increase in HDL was reported.

Red ginseng, 1.5 g three times daily before meals for 7 days, reduced liver cholesterol, decreased theatherogenic index and elevated HDL-cholesterol in 11 patients (5 normal subjects and 6 with hyperlipidaemia). Serum cholesterol was not significantly altered, but serum triglycerides were significantly decreased.

IMMUNOMODULA TION

Ginseng has been shown to significantly enhance NK function in healthy subjects and those suffering from chronic fatigue syndrome or AIDS (P< 0.01).

Ginseng polysaccharide injection has been shown, in a randomised study, to improve immunity in 130 patients with nasopharyngeal carcinoma and to reduce adverse reactions to radiotherapy compared with controls.

Red ginseng powder has been shown to restore immunity after chemotherapy and reduce the recurrence of stage III gastric cancer. The 5-year disease-free survival and overall survival rates were significantly higher in patients taking the red ginseng powder during postoperative chemotherapy versus control (68.2% vs 33.3%, 76.4% vs 38.5%, respectively, P < 0.05). Despite the limitation of a small number of patients (n = 42), these findings suggest that red ginseng powder may help to improve postoperative survival in these patients. Additionally, red ginseng powder may have some immunomodulatory properties associated with CD3 and CD4 activity in patients with advanced gastric cancer during postoperative chemotherapy.

Vaccine adjuvant activity

Ginseng extract (100 mg ginsan G11 5/day) improved the response to an influenza vaccine in a multicentre, randomised, double-blind, placebo-controlled two-arm study of 227 subjects. Compared with vaccine without the ginseng, the addition of ginseng resulted in fewer cases of influenza and common cold. Ginseng increased NK activity and increased antibody production.

The addition of 2 mg ginseng dry extract per vaccine dose has been shown to potentiate the antibody response of commercial vaccines without altering their safety. The enhancing effect of ginseng was demonstrated during the vaccination of pigs against porcine parvovirus and Erysipelothrix rhusiopathiae infections using commercially available vaccines.

COGNITIVE FUNCTION

There is some contention about the benefits of ginseng for improving memory, concentration and learning. Well-controlled clinical trials are lacking and variations in dosage and standardisation may affect study results.

Some studies have demonstrated that ginseng improves the quality of memory and associated secondary memory. In a randomised, placebo-controlled, double-blind, balanced crossover study of healthy, young adult volunteers, 400 mg ginseng was shown to improve secondary memory performance on a Cognitive Drug Research computerised assessment battery and two serial subtraction mental arithmetic tasks. Ginseng also improved attention and the speed of performing the memory tasks. In a later double-blind, placebo controlled, balanced, cross-over study of 30 healthy young adults, acute administration of ginseng (400 mg) was again shown to improve speed of attention.

In a double-blind, placebo-controlled study of healthy young subjects, ginseng extract (G115) improved accuracy and slowed responses during one of two computerised serial subtraction tests (Serial Sevens), and it was also shown to improve mood during these tasks.

In a double-blind, randomised, placebo-controlled 8-9-week trial standardised ginseng extract 400 mg was found significantly to improve abstract thinking (P < 0.005) and reaction time (not significant) in 112 healthy subjects over 40 years of age. Ginseng was found not to affect concentration or memory.

In clinical practice Korean ginseng and Ginkgo biloba are frequently used in combination for cognitive benefits. Combining ginseng with ginkgo dramatically improves memory, concentration and speed of completing mental tasks. In clinical trials ginseng directly modulates cerebroelectrical activity on EEG recordings to a greater extent than Ginkgo biloba.

In a double-blind, placebo-controlled study, post-menopausal women aged 51-66 years were randomly assigned to 12 weeks’ treatment with a combination formula containing 120 mg Ginkgo biloba and 200 mg Panax ginseng (n = 30), or matched placebo (n = 27). The combination appeared to have no effect on mood or cognition after 6 and 12 weeks; however, these doses may be too low. According to other trials it would appear that doses of 400-900 mg of ginseng are required for best results and 200 mg doses have been associated with ‘cognitive costs’, slowing performance on attention tasks.

MENOPAUSAL SYMPTOMS

Korean red ginseng is used to alleviate symptoms associated with menopause; 6 g ginseng for 30 days was shown in a small study of 20 women significantly (P < 0.001) to improve menopausal symptoms, in particular fatigue, insomnia and depression. The women treated had a significant decrease in cortisol and cortisol-to-dehydroepiandrosterone ratio (P < 0.05). No adverse effects were recorded.

ERECTILE DYSFUNCTION

Korean red ginseng has been shown to alleviate erectile dysfunction and improve the ability to achieve and maintain erections even in patients with severe erectile dysfunction. Ginsenosides can facilitate penile erection by directly inducing thevasodilatation and relaxation of the penile corpus cavernosum. Moreover, the effects of ginseng on the corpus cavernosum appear to be mediated by the release and/or modification of release of NO from endothelial cells and perivascular nerves. In men with type 2 diabetes, oxidative stress has been suggested as a contributing factor to erectile dysfunction and animal studies suggest that ginseng can preserve ‘potency’ via its antioxidant effect.

In a double-blind crossover study, 900 mg Korean red ginseng was found to significantly improve the Mean International Index of Erectile Function scores compared with placebo. Significant subjective improvements in penetration and maintenance were reported by participants and penile tip rigidity on the RigiScan showed significant improvement for ginseng versus placebo.

A significant improvement in erectile function, sexual desire, and intercourse satisfaction was demonstrated in 45 subjects following 8 weeks’ oral administration of Korean red ginseng (900 mg three times daily) in a double-blind, placebo-controlled, crossover trial. Subjects demonstrated significant improvement in mean International Index of Erectile Function scores compared with placebo (baseline, 28 ± 16.7; Korean red ginseng, 38.1 ± 16.6; placebo, 30.9 ± 15.7).

QUALITY OF LIFE

An 8-week, randomised, double-blind study found that 200 mg/day ginseng (n = 1 5, placebo: n = 1 5) improved aspects of mental health and social functioning after 4 weeks’ therapy but that these differences disappeared with continued use. A review of eight clinical studies with ginseng found some improvement in QOL scores. However, the findings were equivocal. Despite some positive results, improvement in overall health-related QOL cannot, given the current research, be attributed to Panax ginseng. However, the possibility that various facets of QOL may have improved and the potential of early transient effects cannot be discounted. A double-blind, placebo-controlled, randomised clinical trial of 83 subjects also did not find ginseng to enhance psychological wellbeing in healthy young adults.

A double-blind, placebo-controlled crossover study found that 1200 mg ginseng was only slightly more effective than placebo and not as effective as a good night’s sleep in improving bodily feelings, mood and fatigue in 12 fatigued night nurses. Volunteers slept less and experienced less fatigue but rated sleep quality worse after ginseng administration.

A recent double-blind, placebo-controlled, balanced crossover design of 30 healthy young adults taking Panax ginseng extract (200 mg or 400 mg) or placebo, demonstrated improvements in performance and subjective feelings of mental fatigue during sustained mental activity. It has been hypothesised that this effect may be due in part to the ability of ginseng to regulate blood glucose levels.

ADAPTOGENIC AND TONIC EFFECTS

A randomised double-blind study involving 232 subjects between the ages of 25 and 60 years found that extract equivalent to about 400 mg ginseng root for 4 weeks significantly improved fatigue. Side-effects were uncommon, with only two subjects withdrawing from the study.

A randomised double-blind study of 83 subjects found that extract equivalent to 1 g ginseng root for 4 months decreased the risk of contracting a common cold or bronchitis, improved appetite, sleep, wellbeing and physical performance.

Ginseng is used by many athletes to improve stamina and to facilitate rapid recovery from injuries. To examine the effects of ginseng supplements on hormonal status following acute resistance exercise, eight male college students were randomly given water (control group) or 20 g ginseng root extract treatment immediately after a standardised training exercise. Human growth hormone, testosterone, cortisol, and insulin-like growth factor 1 levels were determined by radioimmunoassay. The responses of plasma hormones following ginseng consumption were not significant between the control and the ginseng groups during the 2-hour recovery period.

Although ginseng is commonly used to improve endurance, a double-blind study of 19 healthy active women found that 400 mg of a ginseng extract (G115) did not improve supramaximal exercise performance or short-term recovery. Analysis of variance using pre-test to post-test change scores revealed no significant difference between the ginseng and placebo study groups for the following variables measured: peak anaerobic power output, mean anaerobic power output, rate of fatigue, and immediate post-exercise recovery heart rates. A recent study by the same authors also failed to find any benefit from ginseng (400 mg/day G11 5; equivalent to 2 g Panax ginseng C.A. Meyer root material for 8 weeks) on improving physical performance and heart rate recovery of individuals undergoing repeated bouts of exhausting exercise.